がん悪液質における亜鉛再分配とホメオスタシス異常

もう1つ、がん悪液質における亜鉛再分配とホメオスタシス異常に関する論文を紹介します。

Pontus M. A. Siren & Matti J. Siren. Systemic zinc redistribution and dyshomeostasis in cancer cachexia. J Cachexia Sarcopenia Muscle (2010) 1:23–33 DOI 10.1007/s13539-010-0009-z

下記のHPでPDF全文見ることができます。

http://www.springerlink.com/content/l4xq3023l2710x05/fulltext.pdf

がん悪液質では急性、慢性の炎症によって亜鉛が骨格筋内に蓄積し、それが蛋白分解系（ubiquitin–proteasome pathway）の活動を亢進させることで、筋萎縮を促進させる可能性があります。一方、他の臓器では亜鉛不足となりその結果、食思不振や全身炎症などが生じるかもしれません。

あくまで仮説ですので今後の検証が必要ですが、亜鉛の再分配とホメオスタシス異常が悪液質の進行に影響を与えている可能性があります。全身性の亜鉛不足の場合は亜鉛（プロマック）を処方すべきだと思いますが、悪液質患者に対する亜鉛の過量投与は問題があるかもしれません。

Abstract

Cachexia affects up to two thirds of all cancer
patients and is a significant cause of morbidity and
mortality. It is a complex metabolic syndrome associated
with the underlying illness and characterized by loss of
skeletal muscle tissue with or without loss of fat mass.
Cachexia’s other prominent clinical symptoms include
anorexia, systemic inflammation, pediatric growth failure,
and hypogonadism. The relationship between the symptoms
of cancer cachexia and the underlying illness is
unclear, and there is an urgent need for a better
understanding of the pathophysiology of this syndrome.
Normal Zn metabolism is often disrupted in cancer
patients, but the possible effects of systemic Zn dyshomeostasis
in cachexia have not been investigated. We
propose that the acute phase response can mediate Zn
redistribution and accumulation in skeletal muscle tissue
and contribute to the activation of the ubiquitin–proteasome
pathway that regulates protein catabolism. This
chronic redistribution deprives Zn from other tissues and
organs and compromises critical physiological functions
in the body. The cardinal symptoms of Zn deficiency are
anorexia, systemic inflammation, growth failure in
children, and hypogonadism. These symptoms also
prominently characterize cancer cachexia suggesting that
the role of systemic Zn dyshomeostasis in cachexia
should be investigated.